Prostaglandins and Aspirin Therapy in Bartter's Syndrome

The Kallikrein-Kinin System in Bartter's Syndrome and Its Response to Prostaglandin Synthetase Inhibition

“…After 4 days of' control observations, a prostaglandin synthetase inhibitor was given. Indomethacin was administered to six patients for 7-9 days, followed by [4][5][6][7] days of posttreatment observations. The dose of indomethacin was 150 mg/day except in two patients, one of whom was given only 112 mg/day because of marked sodium retention; the second vas given only 75 mg/day because she was a 9-yr-old girl who weighed only 17 kg.…”

“…18 of these normal subjects were studied for 1 additional wk after withdrawal of the supplemental NaCl; six of' these normal subjects were repleted and then given a 9-meq sodium diet with indomethacin, 150 mg/day, given on days 5-7 of the diet. Comparisons were made between observations on days [5][6][7] of sodium depletion alone and soditum depletion plus indomethacin.…”

“…This group and others (6,7) have shown that treatment with prostaglandin synthetase inhibitors corrects many of the metabolic and hormonal derangements in the syndrome.…”

Effects of drugs on sodium metabolism.

“…Inhibitors of prostaglandin synthetase, for example indomethacin, produce a fall in urinary prostaglandin excretion and in plasma renin and aldosterone. There is a sustained rise in serum potassium concentration (Verberckmoes et al, 1976;Fichman et al, 1976;Norby et al, 1976;Littlewood, Lee & Meadow, 1978). The determination of urine prostaglandin output may become of more general importance to the clinical pharmacologist as there is already evidence that the angiotension converting enzyme inhibitor captopril may exert part of its effect by increasing intrarenal production of prostaglandins (Swartz et al, 1980 (Kaltreider et al, 1941;Moore, 1946;Forbes & Perley, 1951;Forbes & Lewis, 1956 Following the injection of a dose of radioactive sodium there is first a rapid disappearance of the tracer from the blood, followed by a slower disappearance phase of three to four hours (Figure 1).…”

Bartter's syndrome with normal urinary excretion of prostaglandin E: Therapeutic effects of propranolol, spironolactone, indomethacin and potassium chloride.

“…These include decreased vascular sensitivity to the pressor action of angiotensin II (Bartter et al 1962) and impaired reabsorption of sodium (Cannon et al 1968) or chloride (Gill and Bartter 1978) in the kidney. Recent clinical studies have shown the renomedullary interstitial cell hyperplasia (Verberckmoes et al 1976) and the increases in urinary excretion of prostaglandins (PGs) in this syndrome (Gill et al 1976;Norby et al 1976;Halushka et al 1977). It has also been found that treatment with indomethacin, aspirin or ibuprofen, inhibitors of PG synthetase, corrected functional abnormalities in this syndrome.…”